Fig. 5: Loss of TET2/3 induces profound changes at enhancer regions.

a Boxplot of all LMRs (n = 210,045) identified in wt (n = 3) and dko (n = 3) mice. Boxplot shows the median, the 25th and 75th percentiles, and the smallest and largest values within 1.5× the interquartile range (whiskers). b Pie chart showing the proportion of LMRs that overlap each feature. c Motif analysis of the hypermethylated LMRs (n = 1192) that are associated with significantly reduced gene expression in dko, motifs with the highest scores are listed. P values were calculated using the cumulative hypergeometric distribution (a one-tailed test). d Average histone modification profiles of hypermethylated LMRs. The normalized signal of different histone modifications was measured in a window of ±10,000 base-pair (bp). e Pie chart showing the number of significantly upregulated (red slice) and downregulated (green slice) genes. The highlighted slices represent the proportion of the genes that were associated with hypermethylated LMR (P value was calculated using a two-tailed Fisher’s exact test). f GO analysis of the 216 upregulated genes from (e). The highly enriched biological processes from the enriched categories are shown. g Diseases associated with the 369 downregulated genes associated with hypermethylated LMRs in dko versus wt samples. P values (f, g) were calculated using a two-tailed Fisher’s exact test. h GSEA analysis based on bulk RNA-seq data for intestinal cells from wt and dko mice. Enrichment is shown for interferon-gamma response signature increased in dko mice. Statistics were generated in accordance with the published GSEA algorithm. i, j UMAP and violin plots showing the expression of i Reg3b and j Reg3g in wt and dko samples. In UMAP gene expression projections, red indicates maximum gene expression while blue indicates low or no expression in log-normalized UMI counts. In violin plots, X-axis depicts intestinal cluster subpopulations and Y-axis represents gene expression in log-normalized UMI counts.